Sodium butyrate improves cognitive dysfunction in high-fat diet/ streptozotocin-induced type 2 diabetic mice by ameliorating hippocampal mitochondrial damage through regulating AMPK/PGC-1α pathway.

Autor: Lu LL; Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Department of Pathophysiology, Neuroscience Research Center, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, PR China; Department of Pathology, The Third Hospital of Shijiazhuang, 15 Tiyu South Avenue, Shijiazhuang, 050011, PR China., Liu LZ; Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Department of Pathophysiology, Neuroscience Research Center, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, PR China., Li L; Central Laboratory, The Second Hospital of Hebei Medical University, 215 Heping West Road, Shijiazhuang, 050000, PR China., Hu YY; Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Department of Pathophysiology, Neuroscience Research Center, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, PR China., Xian XH; Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Department of Pathophysiology, Neuroscience Research Center, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, PR China. Electronic address: hebmuxxh@hebmu.edu.cn., Li WB; Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Department of Pathophysiology, Neuroscience Research Center, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, PR China. Electronic address: liwbsjz@hebmu.edu.cn.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2024 Dec 15; Vol. 261, pp. 110139. Date of Electronic Publication: 2024 Sep 02.
DOI: 10.1016/j.neuropharm.2024.110139
Abstrakt: Cognitive dysfunction is an important comorbidity of type 2 diabetes mellitus (T2DM). Sodium butyrate (NaB) is a short-chain fatty acid and has an effect improving T2DM-associated cognitive dysfunction. Using a high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mouse model, the present study investigated the mechanism involved in the beneficial effect of butyrate on diabetic cognitive dysfunction, with a focus on ameliorating mitochondrial damage through regulating the adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α (AMPK/PGC-1α) pathway considering the important role of mitochondrial impairments in the occurrence of T2DM-associated cognitive dysfunction. We found, based on reconfirmation of the improvement of NaB on cognitive impairment, that NaB treatment improved damaged synaptic structural plasticity including the decrease in dendritic spine density and downregulation in the expression of postsynaptic density protein 95 and synaptophysin in the hippocampus in the model mice. NaB treatment also ameliorated mitochondrial ultrastructural damage, increased mitochondrial membrane potential and adenosine 5'-triphosphate content, and improved mitochondrial biogenesis and dynamics in the model mice. Furthermore, the expression of phosphorylated AMPK and PGC-1α was upregulated after NaB treatment in the model mice. In particular, the above beneficial effects of NaB were blocked by the inhibition of either AMPK or PGC-1α. In conclusion, NaB treatment improved cognitive impairment and damaged synaptic structural plasticity in the hippocampus by ameliorating damage to mitochondrial morphology and function through regulating the AMPK/PGC-1α pathway in HFD/STZ-induced T2DM mice.
Competing Interests: Declaration of competing interest We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. All authors have approved the manuscript and agree with submission to Neuropharmacology. The authors have no conflicts of interest to declare.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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